Related Terms

• 2-Oxoglutaric acid, 2-oxopentanedoicic acid, 3-methylhistidine, AAKG, acétoglutarate (French), acide 2-oxoglutarique (French), acide a-cétoglutarique (French), acide alpha-cétoglutarique (French), a-ketoglutaric acid, AKG, alanine, alfa-cetoglutarato (Spanish), alpha keto glutarate, alpha ketoglutarate, alpha KG, alpha-cétoglutarate (French), alpha-cétoglutarate d'arginine (French), alpha-cétoglutarate de calcium (French), alpha-cétoglutarate de créatine (French), alpha-cétoglutarate de glutamine (French), alpha-cétoglutarate de L-arginine (French), alpha-cétoglutarate de L-leucine (French), alpha-cétoglutarate de taurine (French), alpha-ketoacid, alpha-ketoanalogs, alpha-ketoglutarate, alpha-ketoglutarate dehydrogenase (KGDHC), alpha-ketoglutarate-pyridoxine complex, alpha-ketoglutaric acid, alpha-ketoisocaproate, alpha-ketoisovalerate, alpha-ketomethylvalerate, ammonia, arginine, arginine alpha-ketoglutarate, arginine aspartate, calcium alpha-ketoglutarate (Ca-ket), creatine alpha-ketoglutarate (creatine AKG), diarginine alpha-ketoglutarate, glutamate, glutamine, glutamine alpha-ketoglutarate, glycine, histidine, hydroxyproline, L-arginine, L-leucine alpha-ketoglutarate, L-lysine alpha-ketoglutarate reductase, L-ornithine alpha-ketoglutarate, lysine, malate-oxalacetate, ornithine, ornithine alpha-ketoglutarate (OKG), ornithine transcarbamylase, oxoglutarate, phenylalanine, proline, pyridoxine AKG (PAK), pyruvate, pyruvic acid, taurine alpha-ketoglutarate, tyrosine, urea.

Background

• Alpha-ketoglutarate (AKG, also called oxoglutarate) plays an important role in several biological functions.

• AKG has been used for kidney failure, dialysis, and malnutrition.

• Ornithine alpha-ketoglutarate (OAKG or OKG) is made from two amino acids, ornithine and glutamine. It is marketed as a supplement for building muscle. OKG is not specifically discussed in this monograph; it is the topic of a separate monograph.

Scientific Evidence

Tradition/Theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

• Ammonia toxicity, antidote to poisons, antioxidant, athletic performance, bacterial infections, burns, candidiasis (fungal infection), cataracts, chemopreventive (disease-preventing), childhood growth promotion, chronic fatigue syndrome, critical illness, diabetes, energy, functional gastrointestinal disorders, high cholesterol, HIV support, immune function, intestinal problems, kidney disease, malnutrition, muscle atrophy (loss of muscle mass), neurological trauma, osteoporosis, peptic ulcers, stroke recovery, wrinkle prevention (topical).

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

• For dialysis, 1.187 grams of AKG with 0.813 grams of calcium carbonate has been given three times weekly for one year. Also, 4.5 grams of calcium AKG has been given for 36 months.

• For heart protection, 28 grams of AKG has been used during a heart operation. Also, 66 milliliters of AKG solution, at a concentration of 300 grams per liter, was injected into the vein after a heart operation.

Children (under 18 years old)

• There is no proven safe or effective dose for alpha-ketoglutarate in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

• There is no known allergy or sensitivity to alpha-ketoglutarate (AKG).

Side Effects and Warnings

• Alpha-ketoglutarate is generally safe at a dose of 1.187 grams of AKG with 0.813 grams of calcium carbonate given three times weekly for one year. Sixty-six milliliters of AKG solution, at a concentration of 300 grams per liter, injected into the vein, is generally safe.

• Alpha-ketoglutarate is possibly safe, at a dose of 4.5 grams daily of calcium AKG for 36 months, and 0.28 grams of alpha-ketoglutarate per kilogram of body weight after hip replacement surgery is also possibly safe.

• Although alpha-ketoglutarate seems to be well tolerated, a physician should supervise its usage.

• Use cautiously with Lipofundin® (a fat supplement for patients receiving nutrition intravenously) and amino acid supplements.

• Use cautiously in pregnant or breastfeeding women or in children, due to a lack of sufficient safety data.

Pregnancy and Breastfeeding

• Use of alpha-ketoglutarate is not suggested, as there is a lack of scientific evidence on the use of alpha-ketoglutarate during pregnancy or breastfeeding.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

• Alpha-ketoglutarate may interact with cardiovascular agents, dermatologic agents, and agents that damage the liver.

Interactions with Herbs and Dietary Supplements

• Alpha-ketoglutarate may interact with amino acids, cardiovascular herbs and supplements, dermatologic herbs and supplements, herbs and supplements that damage the liver, and herbs and supplements that reduce blood phosphate or phosphorus levels.

Author Information

• This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Blomqvist, B. I., Hammarqvist, F., von der, Decken A., and Wernerman, J. Glutamine and alpha-ketoglutarate prevent the decrease in muscle free glutamine concentration and influence protein synthesis after total hip replacement. Metabolism 1995;44(9):1215-1222. View Abstract

2. Bonnefont, J. P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J. M., and Munnich, A. Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. J.Pediatr. 1992;121(2):255-258. View Abstract

3. Gibson, G. E., Zhang, H., Sheu, K. F., Bogdanovich, N., Lindsay, J. G., Lannfelt, L., Vestling, M., and Cowburn, R. F. Alpha-ketoglutarate dehydrogenase in Alzheimer brains bearing the APP670/671 mutation. Ann.Neurol. 1998;44(4):676-681. View Abstract

4. Hammarqvist, F., Wernerman, J., von der, Decken A., and Vinnars, E. Alpha-ketoglutarate preserves protein synthesis and free glutamine in skeletal muscle after surgery. Surgery 1991;109(1):28-36. View Abstract

5. Jeppsson, A., Ekroth, R., Friberg, P., Kirno, K., Milocco, I., Nilsson, F. N., Svensson, S., and Wernerman, J. Renal effects of alpha-ketoglutarate early after coronary operations. Ann.Thorac.Surg. 1998;65(3):684-690. View Abstract

6. Kjellman, U. W., Bjork, K., Ekroth, R., Karlsson, H., Jagenburg, R., Nilsson, F. N., Svensson, G., and Wernerman, J. Addition of alpha-ketoglutarate to blood cardioplegia improves cardioprotection. Ann.Thorac.Surg. 1997;63(6):1625-1633. View Abstract

7. Kjellman, U., Bjork, K., Ekroth, R., Karlsson, H., Jagenburg, R., Nilsson, F., Svensson, G., and Wernerman, J. Alpha-ketoglutarate for myocardial protection in heart surgery. Lancet 3-4-1995;345(8949):552-553. View Abstract

8. Mason, G. F., Gruetter, R., Rothman, D. L., Behar, K. L., Shulman, R. G., and Novotny, E. J. Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J.Cereb.Blood Flow Metab 1995;15(1):12-25. View Abstract

9. Mastrogiacomo, F. and Kish, S. J. Cerebellar alpha-ketoglutarate dehydrogenase activity is reduced in spinocerebellar ataxia type 1. Ann.Neurol. 1994;35(5):624-626. View Abstract

10. Meissner, T., Mayatepek, E., Kinner, M., and Santer, R. Urinary alpha-ketoglutarate is elevated in patients with hyperinsulinism-hyperammonemia syndrome. Clin.Chim.Acta 2004;341(1-2):23-26. View Abstract

11. Riedel, E., Hampl, H., Steudle, V., and Nundel, M. Calcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations. Miner.Electrolyte Metab 1996;22(1-3):119-122. View Abstract

12. Riedel, E., Nundel, M., and Hampl, H. alpha-Ketoglutarate application in hemodialysis patients improves amino acid metabolism. Nephron 1996;74(2):261-265. View Abstract

13. Wernerman, J., Hammarqvist, F., and Vinnars, E. Alpha-ketoglutarate and postoperative muscle catabolism. Lancet 3-24-1990;335(8691):701-703. View Abstract

14. Wiren, M., Permert, J., and Larsson, J. Alpha-ketoglutarate-supplemented enteral nutrition: effects on postoperative nitrogen balance and muscle catabolism. Nutrition 2002;18(9):725-728. View Abstract

15. Zimmermann, E., Wassmer, S., and Steudle, V. Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism. Miner.Electrolyte Metab 1996;22(1-3):196-199. View Abstract